The design and optimization of chemotherapeutic molecules through molecular modeling is a rapidly growing aspect of drug design. The recent increase in computer power and accompanying decrease in the cost of hardware has led to the wide use of computational chemistry in the development of new drugs. In addition, virtual screening of compound libraries also aids in the rapid development of new drugs. In that regard, there are three computational projects in addition to a project involving the synthesis of potential inhibitors that compile the research presented herein. The first project involves molecular mechanics simulations of isoadenosine analogues as potential inhibitors of S-adenosylhomocysteine hydrolase (SAHase). These analogues possess a carbocyclic moiety at the N-3 position instead of the normal N-9. The second project involves molecular mechanics simulations on flexible nucleosides as bioprobes of biologically significant enzymes. These purine analogues have nucleobases that are separated into their imidazole and pyrimidine rings connected by a single carbon-carbon bond.. This feature imparts flexibility to the base. The third project involves molecular dynamics simulations on expanded purine nucleotides in modified DNA. These compounds possess a heteroaromatic spacer ring inserted between the imidazole and pyrimidine portions of adenosine and guanosine purine rings. These analogues were and are incorporated into 10- and 20-mer DNA strands to investigate the effects on DNA. The final project focuses on the synthesis of a series of chlorinated 3-deazaadenosine analogues as potential anticancer agents. These 3-deazaadenine analogues have chlorine systematically placed in the 2-, 6- and 8-positions of adenine.